Trial record 1 of 1 for:
NCT02398825
Activity and Risk Profile of Ponatinib in Chronic Phase Patients With Chronic Myeloid Leukemia Resistant to Imatinib
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| ClinicalTrials.gov Identifier: NCT02398825 |
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Recruitment Status :
Active, not recruiting
First Posted : March 26, 2015
Last Update Posted : January 5, 2022
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Sponsor:
Gruppo Italiano Malattie EMatologiche dell'Adulto
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
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Brief Summary:
This study aims at evaluating the efficacy of treatment with ponatinib in patients with chronic myeloid leukemia who are in a chronic phase and who previously received treatment with imatinib but resulted to be resistant to it.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Myeloid Leukemia Chronic Phase Adults | Drug: Ponatinib | Phase 2 |
Phase 2, single-arm, multicentre, open label. No interim analysis is planned, but a monitoring committee will evaluate the data every 6 months. Ponatinib is given orally 30 mg daily, with dose adjustment to 15 mg daily once a BCR-ABL1 level smaller or equal to 0.1% (MMR) has been achieved and confirmed in the next test, 4 weeks apart. A return to prior, 30 mg, dose is due in case of return of BCR-ABL1 transcripts level to > 1%. Dose adjustments for toxicity are detailed in the protocol. Treatment time will be 52 weeks, during which study drug will be provided free-of-charge by ARIAD Pharmaceuticals, upon approval of the protocol. Treatment is discontinued at any time in case of failure or treatment-related SAEs. After one year of treatment, upon request of the local investigator and upon confirmation of the Treatment Advisory Committee (TAC, see section 23), ARIAD Pharmaceutics, Inc. will continue to provide ponatinib for the study patients who will benefit from treatment continuation, for at least 2 years, until the drug will be approved with that indication.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 16 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Optimizing Ponatinib USe (OPUS). A GIMEMA Phase 2 Study of the Activity and Risk Profile of Ponatinib, 30 mg Once Daily, in Chronic Myeloid Leukemia (CML) Chronic Phase (CP) Patients Resistant to Imatinib |
| Actual Study Start Date : | June 23, 2016 |
| Actual Primary Completion Date : | February 23, 2021 |
| Estimated Study Completion Date : | February 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Chronic myeloid leukemia
| Arm | Intervention/treatment |
|---|---|
| Experimental: Ponatinib |
Drug: Ponatinib
Ponatinib is given orally 30 mg daily, with dose adjustment to 15 mg daily once a BCR-ABL1 level minor or equal to 0.1% (MMR) has been achieved and confirmed in the next test, 4 weeks apart. A return to prior, 30 mg, dose is due in case of return of BCR-ABL1 transcripts level to > 1%. Dose adjustments for toxicity are detailed in the protocol. |
Primary Outcome Measures :
- Number of patients with major cytogenetic response [ Time Frame: After 52 weeks of ponatinib treatment start ]
Cytogenetic response (CyR) is defined based on the percentage of Ph pos metaphases, as evaluated by chromosome banding analysis (CBA) of at least 20 marrow cell metaphases:
- Major Cytogenetic Response if Ph pos metaphases < 35%
- Complete (CCyR) if Ph pos metaphases 0 or FISH BCR-ABL1 nuclei minor or equal to 1%
- Partial (PCyR) if Ph pos metaphases 1-34%
- Minor (mCyR) if Ph pos metaphases 35-65%
- Minimal or none (min/none CyR) if Ph pos metaphases > 65% If marrow cell metaphases cannot be obtained or analysed, interphase fluorescence-in-situ-hybridization (FISH) can be used, but only to distinguish a CCyR (minor or equal to 1% positive nuclei out of at least 200 nuclei) from a non CCyR. FISH data cannot be used to classify a response as minimal, minor, or partial.
Secondary Outcome Measures :
- Number of Cardiovascular Adverse Events (AEs) [ Time Frame: After three years from ponatinib treatment start ]
- Number of blood hypertension AEs [ Time Frame: After three years from ponatinib treatment start ]
- Number of pancreatitis AEs [ Time Frame: After three years from ponatinib treatment start ]
- Number of patients achieving Complete Cytogenetic Response (CCyR) [ Time Frame: After 52 weeks of ponatinib treatment start ]
- Number of patients achieving major molecular response [ Time Frame: After 52 weeks of ponatinib treatment start ]
- Number of patients with failure-free survival [ Time Frame: At 36 months from ponatinib treatment start ]
- Number of patients with progression-free survival [ Time Frame: At 36 months from ponatinib treatment start ]
- Number of patients in overal survival [ Time Frame: At 36 months from ponatinib treatment start ]
- Number of patients in event-free survival [ Time Frame: At 36 months from ponatinib treatment start ]
- Quality of Life patterns over time with the EORTC QLQ-C30 and the EORTC QLQ-CML24 questionnaires [ Time Frame: At baseline and at at weeks 4, 12, 24, 36 and 52 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Cytogenetic and/or molecular confirmed diagnosis of Ph+ and/or BCR-ABL1+ CML
- Age ≥ 18 years
- Chronic phase CML
- Prior treatment with imatinib, any dose
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Resistance to imatinib, as defined by any one of the ELN 2013 failure criteria, as follows:
- no complete hematologic response (CHR) at 3 months
- no cytogenetic response (CyR) (Ph+ > 95%) at 3 months
- Less than partial CyR (PCyR, Ph+ > 35%) at 6 months
- BCR-ABL1 > 10% at 6 months
- Non complete CyR (CCyR) (Ph+ > 0%) at 12 months
- BCR-ABL1 > 1% at 12 months
- Loss of CHR, at any time
- Loss of CCyR, at any time
- Confirmed loss of major molecular response (MMR) (BCR-ABL1 bigger or equal to 0.1% in two consecutive tests, of which one bigger or equal to 1%), at any time
- Any new BCR-ABL1 mutation, at any time
- For females of childbearing potential, a negative pregnancy test must be documented prior to enrolment
- An effective form of contraception with their sexual partners from enrolment through 4 months after the end of treatment
- Signed written informed consent according to ICH/EU/GCP and national local laws prior to any study procedures
- Willingness and ability to comply with scheduled visits and study procedures.
Exclusion Criteria:
- Accelerated or blastic phase CML
- Patients previously treated with nilotinib or dasatinib
- Patients with the T315I mutation
- History of acute pancreatitis within 1 year of study or history of chronic pancreatitis or of alcohol abuse
- Patients with history of acute myocardial infarction (AMI), unstable angina or coronary heart disease (CHD), congestive heart failure, cerebrovascular events (CVE) (stroke or transitory ischemic attack), or peripheral artery occlusive disease (PAOD)
- Compelled to take medications that are known to be associated with Torsades de Pointes and/or with significant QTc prolongation
- Pregnant or breastfeeding
- Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the drug
- Lack of informed consent
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02398825
Locations
Show 37 study locations
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
| Study Chair: | Fausto Castagnetti | Department of Hematology, S. Orsola-Malpighi University of Bologna |
Additional Information:
| Responsible Party: | Gruppo Italiano Malattie EMatologiche dell'Adulto |
| ClinicalTrials.gov Identifier: | NCT02398825 |
| Other Study ID Numbers: |
CML1315 2015-001102-34 ( EudraCT Number ) |
| First Posted: | March 26, 2015 Key Record Dates |
| Last Update Posted: | January 5, 2022 |
| Last Verified: | August 2021 |
Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
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Chronic myeloid leukemia Chronic phase Adults Ponatinib Imatinib resistant |
Additional relevant MeSH terms:
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Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Neoplasms by Histologic Type Neoplasms Myeloproliferative Disorders Bone Marrow Diseases |
Hematologic Diseases Ponatinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |